This is an application for a FIRST award from a new investigator at the Jackson Laboratory who seeks support for genetic analysis of the piebald deletion in the mouse. Specifically, he plans to focus on genes whose absence results in spinal cord malformation and homeotic transformations of the axial skeleton. The long term objectives of this work are to identify genes important in mammalian embryogenesis and to investigate the relationships that exist between genome organization and the genetic control of development. Three specific aims are outlined: 1) to determine whether a relationship exists between the 15DttMb and 36Pub phenotypes and the roles played by retinoic acid and the Hox genes in pattern formation; 2) to develop genetic and physical resources for functional genomic studies of defined chromosomal intervals within the 15DttMb and 36Pub deletions; 3) to clone and characterize genes corresponding to the 15DttMb functional interval, which is associated with hydrocephalus and respiratory failure, as well as homeotic transformation of vertebrae, and spinal cord malformations.